Batch and Flow Green Microwave-Assisted Catalytic Conversion Of Levulinic Acid to Pyrrolidones.

This paper reports a new sustainable protocol for the microwave-assisted catalytic conversion of levulinic acid into N-substituted pyrrolidones over tailor-made mono (Pd, Au) or bimetallic (PdAu) catalysts supported on either highly mesoporous silica (HMS) or titania-doped HMS, exploiting the advantages of dielectric heating. MW-assisted reductive aminations of levulinic acid with several amines were first optimized in batch mode under hydrogen pressure (5 bar) in solvent-free conditions. Good-to-excellent yields were recorded at 150 °C in 90 min over the PdTiHMS and PdAuTiHMS, that proved recyclable and almost completely stable after six reaction cycles. Aiming to scale-up this protocol, a MW-assisted flow reactor was used in combination with different green solvents. Cyclopentyl methyl ether (CPME) provided a 99 % yield of N-(4-methoxyphenyl) pyrrolidin-2-one at 150 °C over PdTiHMS. The described MW-assisted flow synthesis proves to be a safe procedure suitable for further industrial applications, while averting the use of toxic organic solvents.

Microwave-Assisted Protocol for Green Functionalization of Thiophenes With a Pd/ß-Cyclodextrin Cross-Linked Nanocatalyst.

Microwaves (MW) are often the most efficient, in terms of heat exchange and conversion rate, of all the energy sources used to promote chemical reactions thanks to fast volumetric dielectric heating, and metal-catalyzed synthetic reactions under heterogeneous conditions are an eloquent example. We herein report a MW-assisted green protocol for the C-H arylation of thiophenes with substituted aryl halides. This sustainable protocol carried out in γ-valerolactone (GVL) is catalyzed by Pd nanoparticles embedded in cross-linked ß-cyclodextrin. In view of the excellent results achieved with activated substrates, the one-pot synthesis of a 4(3H)-quinazolinone derivative has been accomplished. A pressure-resistant MW reactor, equipped with multiple gas inlets, was used for sequential (i) C-H arylation, (ii) reduction, and (iii) carbonylation in the presence of the same catalyst, but under different gas atmospheres. The robust heterogeneous Pd catalyst showed limited metal leaching in GVL, making this an efficient MW-assisted process with high atom economy.

Cross-Linked Cyclodextrins Bimetallic Nanocatalysts: Applications in Microwave-Assisted Reductive Aminations.

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H2 or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a ß-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H2. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H2 pressure. The formation of a CuxPdy alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields.

Microwave-Assisted Dehydrogenative Cross Coupling Reactions in γ-valerolactone with a Reusable Pd/ß-cyclodextrin Crosslinked Catalyst.

Transition-metal mediated C⁻H bond activation and functionalization is one of the most straightforward and powerful tools in modern organic synthetic chemistry. Oxidative C⁻H/C⁻H coupling reactions between two (hetero)arenes under heterogeneous catalysis may be a valuable means for the production of a plethora of bi(hetero)aryls, and one that adheres to the increasing demand for atom-economic and sustainable chemistry. We have therefore developed a reusable heterogeneous catalytic system, which is based on Pd cross-linked ß-cyclodextrin, to perform an efficient microwave-assisted oxidative C⁻H/C⁻H cross coupling process between benzothiazoles and methyl thiophene in the presence of green solvents.